A successful narcotic antagonist has been sought for two decades. The discoveries of the antagonists cyclozocine and naloxone have led to accelerated research in the area. A more recent antagonist, naltrexone, has been shown to be an effective antagonist based on extensive clinical experiments. It is also desirable to obtain a long-acting drug, thus alleviating the need for an addicted person to take regular medication and provide maximum efficacy with minimum dose. Several attempts have been made to develop drug delivery systems capable of providing long-acting narcotic antagonistic effects. They have not been succaessful in achieving constant release due to the fact that drug concentration is depleted upon prolonged release. Our approach to controlled release is based on a biodegradable polymer backbone to which drug molecules are covalently bound via labile groups. Drug release is primarily controlled by the rate of hydrolysis of the labile bonds, not by a diffusion process. The polymer backbone breaks down much more slowly than the polymer-drug labile bond over a period of months. Immune reactions in animals caused by these polymer backbones and degraded fragments were found to be minimal. Initial studies in our laboratory are supportive of this claim. This proposal includes the use of the narcotic antagonist naltrexone and various polyamino acids as backbone drug carriers. The basic studies aim for the attainment of a constant release rate in both in vitro and in vivo animal experiments using various combinations of polyamino acid backbones, spacer groups and labile bonds. The data obtained from the proposed studies would provide information valuable in the design of long-term, hypodermically injectable, biodegradable naltrexone delivery systems.